What Is the Evidence for Changes in Cognition and Functioning Over the Lifespan in Patients With Schizophrenia?

Philip D. Harvey, PhD

Cognitive deficits in schizophrenia are important predictors of impairment in most functional domains and are a critical therapeutic target.1 These deficits typically appear at or before the onset of illness,2 are stable across time in most patients,3 appear to worsen predominantly in the oldest patients,4 and can be improved by cognitive remediation treatments.5 Recent evidence, however, suggests that cognitive function does not necessarily follow a pattern of age-related decline.

Evidence of Changes in Cognition and Functioning Across the Lifespan

The course of cognitive function was evaluated in a large-scale cross-sectional study6 assessing institutionalized schizophrenia patients ranging from 25 to 95 years old. Patients with schizophrenia exhibited evidence of decline in cognitive function, with a 3 point per decade difference in Mini-Mental State Examination (MMSE) functioning.

In a related study,7 the cognitive, clinical, and functional characteristics of chronic schizophrenia were examined in 3 samples of patients. One included long-term institutionalized patients, another included long-term institutionalized patients previously discharged to nursing home care, and the third was an acutely admitted sample with < 6 weeks of institutionalization. Results indicated that severity of psychotic symptoms was essentially identical in the 3 groups. Acutely admitted patients had dramatically higher cognitive and adaptive function than those who were chronically institutionalized.

Do These Data Implicate Cognitive Decline?

These data elicited a debate as to whether these cognitive deficits are neurodevelopmental in origin and thus static over time. In a study8 addressing this question, chronically hospitalized patients > 65 years were followed for 5 years. Results indicated a 48% risk of worsening across the 60-month assessment period. Although this difference was significant, the amount of change in each individual patient over the 5-year period was not dramatic, equivalent to a decline of approximately 3 MMSE points.

A longitudinal study9 from that research effort examined healthy individuals, people with Alzheimer’s disease, and people with schizophrenia to determine whether there was evidence of an age-associated risk of worsening. Results indicated healthy individuals lost an average of 1 MMSE point over the 6-year follow-up period, reflecting minimal cognitive change, with Alzheimer’s disease patients losing 10–14 points. Schizophrenia patients had a pattern of worsening distinctly associated with age. For the schizophrenia patients who were 50 to 64 years of age, there was a minimal risk of worsening (0.5 MMSE points/year). For older schizophrenia patients, the risk of worsening was substantially greater, with an inflection point at age 65. Conclusions from this study were that, though this sample very likely is not reflective of community care, these findings are relevant to understanding the functioning of poor-outcome patients.

Cognitive and functional decline was examined in ambulatory schizophrenia patients with inpatient stays varying from 4 weeks to 36 years.10 Every patient in the study was followed for up to 40 months and was assessed on up to 2 occasions after baseline. Data were gathered on functional capacity using the UCSD Performance-Based Assessment (UPSA), and the Social Skills Performance Assessment (SSPA). Additionally, everyday function was assessed with the Specific Levels of Functioning (SLOF) measure, a rating scale aimed at social, vocational, and residential function. A mixed-model repeated measures analysis determined that the ability to perform everyday living skills was worse in patients with an extended institutional stay.10 Conversely, patients with no long-term hospitalization demonstrated improvements in functional capacity that were quite likely attributable to practice effects. Conclusions from these data indicated a potential institutionalization cutoff point of 6 months that delineated decline versus improvement.10 Patients clustering around this time point demonstrated no evidence of worsening in performance-based assessments of functioning.

Since that publication, these analyses were expanded to include measures of real-world outcomes.11 Results indicated that everyday functioning (SLOF) experienced a decline over time (AV 1).11 Overall, these data suggested that as the UPSA and SSPA deteriorated, there was a corresponding deterioration in everyday functioning.

AV 1. Specific Levels of Functioning (SLOF) Everyday Functioning Scores Over 3 Assessments (00:48)


One of the clear implications of these results was that direct intervention on cognition and functional capacity should be strongly considered. Cognitive remediation and skills training interventions have been shown to improve cognition and functioning12 and to be effective even in some of the most intractable patients.13 Additionally, these data suggested that reducing the risk factors for cortical deterioration, such as extended periods of psychosis, may represent a complementary approach. Finally, these interventions may reduce the subtle progressive cognitive changes seen in some of these patients.

  1. Buchanan RW, Davis M, Goff D, et al. Schizophr Bull. 2005;31(1):5–19. doi:10.1093/schbul/sbi020 PubMed
  2. Seidman LJ, Giuliano AJ, Meyer EC, et al. Arch Gen Psychiatry. 2010;67(6):578–588. doi:10.1001/archgenpsychiatry.2010.66 PubMed
  3. Heaton RK, Gladsjo JA, Palmer BW, et al. Arch Gen Psychiatry. 2001;58(1):24–32. doi:10.1001/archpsyc.58.1.24 PubMed
  4. Loewenstein DA, Czaja SJ, Bowie CR, et al. Am J Geriatr Psychiatry. 2012;20(1):29–40. doi:10.1097/JGP.0b013e31823bc08c PubMed
  5. Kurtz MM, Seltzer JC, Fujimoto M, et al. Schizophr Res. 2009;107(2-3):267–274. doi:10.1016/j.schres.2008.10.014 PubMed
  6. Davidson M, Harvey PD, Powchik P, et al. Am J Psychiatry. 1995;152(2):197–207. PubMed
  7. Harvey PD, Howanitz E, Parrella M, et al. Am J Psychiatry. 1998;155(8):1080–1086. PubMed
  8. Harvey PD, Davidson M. In: Davis KL, Charney D, Coyle JT, et al, eds. Neuropsychopharmacology: Fifth Generation of Progress. Philadelphia, PA: Lippincott; 2002:641–655.
  9. Friedman JI, Harvey PD, Coleman T, et al. Am J Psychiatry. 2001;158(9):1441–1448. doi:10.1176/appi.ajp.158.9.1441 PubMed
  10. Harvey PD, Reichenberg A, Bowie CR, et al. Biol Psychiatry. 2010;67(10):933–939. doi:10.1016/j.biopsych.2010.01.008 PubMed
  11. Reichenberg A, Feo C, Prestia D, et al. Everyday functioning in schizophrenia: the longitudinal course and correlates. Schizophr Res: Cogn. In press.
  12. Wykes T, Huddy V, Cellard C, et al. Am J Psychiatry. 2011;168(5):472–485. doi:10.1176/appi.ajp.2010.10060855 PubMed
  13. Lindenmayer JP, McGurk SR, Mueser KT, et al. Psychiatr Serv. 2008;59(3):241–247. doi:10.1176/ PubMed
Philip D. Harvey, PhD

Philip D. Harvey, PhD

University of Miami Miller School of Medicine, Miami, Florida

This Brief Report is derived from the roundtable meeting “Understanding the lifetime course of schizophrenia: a longitudinal perspective on neurobiology to promote better outcomes and recovery,” which was held October 15, 2013. The author acknowledges Healthcare Global Village for editorial assistance in developing the manuscripts.

The meeting, manuscript preparation, and dissemination of this brief report were supported by Otsuka America Pharmaceutical, Inc., and Lundbeck. All faculty received a fee for service from Otsuka America Pharmaceutical, Inc., and Lundbeck for participation in the meeting and preparation of the manuscripts.

Faculty Disclosure

Dr Harvey received a fee for service from Otsuka America Pharmaceutical, Inc., and Lundbeck for participation in the meeting and preparation of this manuscript and, during the past year, has received consulting fees from Abbvie, Boehringer-Ingleheim, En Vivo, Forest, Genentech, Otsuka America Pharmaceutical, Inc., Sunovion, and Takeda.


The opinions expressed herein are those of the authors and do not necessarily reflect the opinions of the publisher, the American Society of Clinical Psychopharmacology, Healthcare Global Village, or the commercial supporters.

doi: 10.4088/JCP.13065br4

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